In industry and biology it is often advantageous to capture particulate material from a sample suspension on a filter for purification, enrichment, observation or subsequent analysis. Once a desired amount of material is captured on a filter, it is sometimes advantageous to deposit an approximate monolayer of this material on a receiving surface for analysis, for example, biological cells may be captured on a membrane filter for deposition on a microscope slide for microscopic analysis.
As used herein, “sample suspension” means particulate material suspended in a liquid or gas. “Material” as used herein means biological cells, organisms, bacteria, viruses, or components of these, as well as organic and inorganic particulates or any other matter which may be captured or isolated on a filter. This captured material may provide diagnostic and/or analytical information or be re-suspended or otherwise used. For example, captured material may be analyzed chemically or may be placed on a receiving surface, such as a microscope slide for analysis.
The term “microscopic analysis” as used herein means a process wherein a microscope under human and/or machine control is used for visualization, analysis, and/or enumeration, and/or categorization, and/or photography, and/or electronic image acquisition of biological or other material. “Receiving surface” as used herein, means all discrete objects which serve as substrates to support material, for example a microscope slide, cover-glass, plastic sheet, semiconductor chip, strip of tape, etc.
The quantity and characteristics of particulate materials are important in manufacturing, for example, processes that utilize powders, pigments, fuels or lubricants. Particle evaluations are also used to assess contaminants in water or air such as pollen, asbestos and soot. Particulate material is sometimes used indirectly to assess proteins or chemicals, where it acts as a support medium, for example, beads coated with monoclonal antibody may be interacted with blood. Then these reacted beads may be captured on a filter and assessed for bound proteins or chemicals.
For a subset of applications that utilize filter capture, it is advantageous to work with a known or desired amount of material. Certain chemical methods, for example, rely on tightly controlled amounts of materials. Similarly, the concentration of material deposited on a receiving surface for microscopic analysis influences observation and analysis. When an excessive amount of material is deposited, microscopic analysis may be complicated, for example, when folding or overlapping material obscures adjacent material. Conversely, a well-formed monolayer of sparse material may also impede effective microscopic analysis by: extending the time required to locate material, reducing the ability to compare material within a field of view, diluting the diagnostic content or otherwise undermining effective analysis. “Monolayer” as used herein means a substantially two-dimensional, relatively uniformly distributed layer of material deposited on a receiving surface. For cytological applications, this material is predominately comprised of single cells and cell clusters. For some biological applications addition efforts are made to minimize the number of cells clusters. To accomplish this task, physical agitation and/or a disaggregating agent may be used to help disperse cells from tissue sections, clumps, or otherwise break-up and dissolve mucus components which are relatively common in cytological scrapings or lung sputum samples. Other applications, such as detecting malignancy-associated changes that rely on assessing DNA and DNA distribution, primarily in cell nuclei, benefit when a desired amount of material is present.
For some applications, controlling the amount of material deposited begins with assessing and adjusting the concentration of material in the sample suspension. Particle counters based on electrical impedance, light scatter, turbidity or other principles are often used to measure the concentration of material in suspension. Centrifugation, cell sorters, magnetic-beads, columns, density gradients, dilutions or other means may be used alone or in combination with these measurement methods to increase, decrease or otherwise adjust the concentration of material in a sample suspension. Once the sample concentration is known, or adjusted to a desired level, a controlled volume or set collection time could be used to gauge the amount of material captured on a filter.
Additionally, apparatus and methods are available to capture a material on a filter for monolayer deposition, however, controlling the amount of material collected on a filter is more difficult to achieve. Apparatus which provides for capturing a desired amount of material on a filter tend to be: relatively complex, expensive, require electronic control, are difficult to automate or are otherwise limited.
Therefore, a simple, reliable method of capturing a desired amount of material on a filter for monolayer deposition or other uses would be advantageous. The present invention is a filter device that provides a means to capture a desired amount of material from a sample suspension. To accomplish this, a pressure sensor is used substantially to monitor the flow rate of sample suspension through the filter and a separate or integrated valve further provides a means to control the sample flow rate and thus the collection of material. Once a desired amount of material is captured on a filter, such as a membrane with uniform, distributed pores, it may be transferred by contact to a receiving surface for observation or analysis.